Comparison of available iron chelators to an ideal chelation drug
. | “Ideal chelator” . | Deferoxamine . | Deferiprone . | Deferasirox . |
|---|---|---|---|---|
| Route of administration | Oral | Parenteral, usually subcutaneous or intravenous | Oral | Oral |
| Plasma half-life | Long enough to give constant protection from labile plasma iron | Short (minutes); requires constant delivery | Moderate (< 2 hours). Requires at least 3-times-per-day dosing | Long, 8-16 hours; remains in plasma at 24 h |
| Therapeutic index | High | High at moderate doses in iron-overloaded subjects | Idiosyncratic side effects are most important | Probably high in ironoverloaded subjects* |
| Molar iron chelating efficiency; charge of iron (III) complex | High, uncharged | High (hexadentate); charged | Low (bidentate); uncharged | Moderate (tridentate); uncharged |
| Important side effects | None or only in iron-depleted subjects | Auditory and retinal toxicity; effects on bones and growth; potential lung toxicity, all at high doses; local skin reactions at infusion sites | Rare but severe agranulocytosis; mild neutropenia; common abdominal discomfort; erosive arthritis | Abdominal discomfort; rash or mild diarrhea upon initiation of therapy; mild increased creatinine level |
| Ability to chelate intracellular cardiac and other tissue iron in humans | High | Probably lower than deferiprone and deferasirox | High in clinical and in vitro studies | Insufficient clinical data available; promising in laboratory studies |
. | “Ideal chelator” . | Deferoxamine . | Deferiprone . | Deferasirox . |
|---|---|---|---|---|
| Route of administration | Oral | Parenteral, usually subcutaneous or intravenous | Oral | Oral |
| Plasma half-life | Long enough to give constant protection from labile plasma iron | Short (minutes); requires constant delivery | Moderate (< 2 hours). Requires at least 3-times-per-day dosing | Long, 8-16 hours; remains in plasma at 24 h |
| Therapeutic index | High | High at moderate doses in iron-overloaded subjects | Idiosyncratic side effects are most important | Probably high in ironoverloaded subjects* |
| Molar iron chelating efficiency; charge of iron (III) complex | High, uncharged | High (hexadentate); charged | Low (bidentate); uncharged | Moderate (tridentate); uncharged |
| Important side effects | None or only in iron-depleted subjects | Auditory and retinal toxicity; effects on bones and growth; potential lung toxicity, all at high doses; local skin reactions at infusion sites | Rare but severe agranulocytosis; mild neutropenia; common abdominal discomfort; erosive arthritis | Abdominal discomfort; rash or mild diarrhea upon initiation of therapy; mild increased creatinine level |
| Ability to chelate intracellular cardiac and other tissue iron in humans | High | Probably lower than deferiprone and deferasirox | High in clinical and in vitro studies | Insufficient clinical data available; promising in laboratory studies |
Nephrotoxicity observed in non—iron-loaded animals has been minimal in iron-overloaded humans, but effectiveness is demonstrated only at higher end of tested doses, as discussed in Cappellini et al.1